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Leishmania infection modulates beta-1 integrin activation and alters the kinetics of monocyte spreading over fibronectin.

Figueira CP, Carvalhal DG, Almeida RA, Hermida Md, Touchard D, Robert P, Pierres A, Bongrand P, dos-Santos WL - Sci Rep (2015)

Bottom Line: Contact with Leishmania leads to a decreases in mononuclear phagocyte adherence to connective tissue.This cytoplasm spread was inhibited using an anti-VLA4 blocking antibody.These changes in phagocyte function may be important for parasite dissemination and distribution of lesions in leishmaniasis.

View Article: PubMed Central - PubMed

Affiliation: Fundação Oswaldo Cruz-Bahia, Centro de Pesquisas Gonçalo Moniz, Brazilian Ministry of Health, Salvador, Brazil.

ABSTRACT
Contact with Leishmania leads to a decreases in mononuclear phagocyte adherence to connective tissue. In this work, we studied the early stages of bond formation between VLA4 and fibronectin, measured the kinetics of membrane alignment and the monocyte cytoplasm spreading area over a fibronectin-coated surface, and studied the expression of high affinity integrin epitope in uninfected and Leishmania-infected human monocytes. Our results show that the initial VLA4-mediated interaction of Leishmania-infected monocyte with a fibronectin-coated surface is preserved, however, the later stage, leukocyte spreading over the substrate is abrogated in Leishmania-infected cells. The median of spreading area was 72 [55-89] μm(2) for uninfected and 41 [34-51] μm(2) for Leishmania-infected monocyte. This cytoplasm spread was inhibited using an anti-VLA4 blocking antibody. After the initial contact with the fibronectrin-coated surface, uninfected monocyte quickly spread the cytoplasm at a 15 μm(2) s(-1) ratio whilst Leishmania-infected monocytes only made small contacts at a 5.5 μm(2) s(-1) ratio. The expression of high affinity epitope by VLA4 (from 39 ± 21% to 14 ± 3%); and LFA1 (from 37 ± 32% to 18 ± 16%) molecules was reduced in Leishmania-infected monocytes. These changes in phagocyte function may be important for parasite dissemination and distribution of lesions in leishmaniasis.

No MeSH data available.


Related in: MedlinePlus

Monocyte adhesion under flow.Monocytes cultured alone or with Leishmania were driven along fibronectin-coated surfaces in a laminar flow chamber in medium alone or in medium containing 10 mM MnCl2. The trajectories of the individual cells were monitored for 2 min for quantitative determination of the number of total detectable arrests with durations between ∼200 ms and 2 min.
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f1: Monocyte adhesion under flow.Monocytes cultured alone or with Leishmania were driven along fibronectin-coated surfaces in a laminar flow chamber in medium alone or in medium containing 10 mM MnCl2. The trajectories of the individual cells were monitored for 2 min for quantitative determination of the number of total detectable arrests with durations between ∼200 ms and 2 min.

Mentions: To identify Leishmania-induced changes in the VLA4-mediated rolling of monocytes, we used an in vitro model of laminar flow to compare this adhesion step in uninfected and Leishmania-infected cells. Leishmania-infected monocytes displayed numerous transient arrests, with a frequency comparable with that found for uninfected monocytes (Fig. 1). After Mn++ stimulation, the frequency of arrests increased in both uninfected and Leishmania-infected monocytes. Taken together, these results demonstrate that Leishmania infection did not interfere with VLA4-mediated monocyte rolling or initial binding to fibronectin.


Leishmania infection modulates beta-1 integrin activation and alters the kinetics of monocyte spreading over fibronectin.

Figueira CP, Carvalhal DG, Almeida RA, Hermida Md, Touchard D, Robert P, Pierres A, Bongrand P, dos-Santos WL - Sci Rep (2015)

Monocyte adhesion under flow.Monocytes cultured alone or with Leishmania were driven along fibronectin-coated surfaces in a laminar flow chamber in medium alone or in medium containing 10 mM MnCl2. The trajectories of the individual cells were monitored for 2 min for quantitative determination of the number of total detectable arrests with durations between ∼200 ms and 2 min.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4528201&req=5

f1: Monocyte adhesion under flow.Monocytes cultured alone or with Leishmania were driven along fibronectin-coated surfaces in a laminar flow chamber in medium alone or in medium containing 10 mM MnCl2. The trajectories of the individual cells were monitored for 2 min for quantitative determination of the number of total detectable arrests with durations between ∼200 ms and 2 min.
Mentions: To identify Leishmania-induced changes in the VLA4-mediated rolling of monocytes, we used an in vitro model of laminar flow to compare this adhesion step in uninfected and Leishmania-infected cells. Leishmania-infected monocytes displayed numerous transient arrests, with a frequency comparable with that found for uninfected monocytes (Fig. 1). After Mn++ stimulation, the frequency of arrests increased in both uninfected and Leishmania-infected monocytes. Taken together, these results demonstrate that Leishmania infection did not interfere with VLA4-mediated monocyte rolling or initial binding to fibronectin.

Bottom Line: Contact with Leishmania leads to a decreases in mononuclear phagocyte adherence to connective tissue.This cytoplasm spread was inhibited using an anti-VLA4 blocking antibody.These changes in phagocyte function may be important for parasite dissemination and distribution of lesions in leishmaniasis.

View Article: PubMed Central - PubMed

Affiliation: Fundação Oswaldo Cruz-Bahia, Centro de Pesquisas Gonçalo Moniz, Brazilian Ministry of Health, Salvador, Brazil.

ABSTRACT
Contact with Leishmania leads to a decreases in mononuclear phagocyte adherence to connective tissue. In this work, we studied the early stages of bond formation between VLA4 and fibronectin, measured the kinetics of membrane alignment and the monocyte cytoplasm spreading area over a fibronectin-coated surface, and studied the expression of high affinity integrin epitope in uninfected and Leishmania-infected human monocytes. Our results show that the initial VLA4-mediated interaction of Leishmania-infected monocyte with a fibronectin-coated surface is preserved, however, the later stage, leukocyte spreading over the substrate is abrogated in Leishmania-infected cells. The median of spreading area was 72 [55-89] μm(2) for uninfected and 41 [34-51] μm(2) for Leishmania-infected monocyte. This cytoplasm spread was inhibited using an anti-VLA4 blocking antibody. After the initial contact with the fibronectrin-coated surface, uninfected monocyte quickly spread the cytoplasm at a 15 μm(2) s(-1) ratio whilst Leishmania-infected monocytes only made small contacts at a 5.5 μm(2) s(-1) ratio. The expression of high affinity epitope by VLA4 (from 39 ± 21% to 14 ± 3%); and LFA1 (from 37 ± 32% to 18 ± 16%) molecules was reduced in Leishmania-infected monocytes. These changes in phagocyte function may be important for parasite dissemination and distribution of lesions in leishmaniasis.

No MeSH data available.


Related in: MedlinePlus